Diclofenac and its salts possess excellent antiphlogistic, analgesic, antipyretic activities, and are widely used for treating various inflammatory diseases, such as acute and chronic rheumatoid arthritis, osteoarthritis, and the like. They are typically formulated for oral administration, as a suppository, in an ointment, or the like.
For these preparations, however, i.e., oral dosage forms, suppositories, and ointments, the pharmaceutical effects fluctuate due to differences between the amount of drug administered and the amount of drug absorbed by the body. In addition, these preparations require a certain period of time for the active components to exhibit their effects because of a time-lag between the administration and absorption. Therefore, intravenous or intramuscular administration is desirable to obtain immediate antiphlogistic, analgesic, or antipyretic effects in the case of serious symptoms requiring an urgent treatment, e.g., for effecting an anti-inflammatory or analgesic action after an operation or injury, or visceral pain associated with an attack, cancer, or the like.
For these reasons parenteral preparations comprising diclofenac and/or its salt have been developed. These compositions comprise diclofenac, its salt, or both, and an alcohol, such as propylene glycol, benzyl alcohol, or the like, and water. These conventional parenteral preparations containing diclofenac and/or its salt have the following side effects. First, they produce pain at the injection site during injection. Second, they induce side effects, such as precordial anxiety, ague, cold sweat, breathing difficulty, numbness of extremities, and the like, due to the rapid increase in drug concentration in the plasma immediately after the injection. In addition, the therapeutic effect of these conventional injectable preparations lasts for a short period of time because the drug is eliminated from the plasma quickly.
The present inventors, therefore, have developed antiphlogistic, analgesic, antipyretic parenteral preparations comprising diclofenac, its salt, or both, which gives reduced side effects upon parenteral administration. Moreover, these new parenteral preparations sustain the release of the drug to achieve long-lasting therapeutic effects.